| 1. |
- Daniel, Maria, et al.
(författare)
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Effect of Myocardial Infarction With Nonobstructive Coronary Arteries on Physical Capacity and Quality-of-Life
- 2017
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 120:3, s. 341-346
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Tidskriftsartikel (refereegranskat)abstract
- Patients with myocardial infarction with nonobstructive coronary arteries (MINOCA), including Takotsubo syndrome (TS), are considered to have a better survival compared with those with coronary heart disease (CHD). Studies of patients with MINOCA measuring physical and mental function including matched control groups are lacking. The aim of this study was to determine the physical capacity and quality of life in patients with MINOCA. One-hundred patients with MINOCA along with TS (25%) were investigated from 2007 to 2011. A bicycle exercise stress test was performed 6 weeks after hospitalization and QoL was investigated by the Short Form Survey 36 at 3 months' follow-up. Both a healthy and a CHD group that were age and gender matched were used as controls. The MINOCA group had a lower physical capacity (139 ± 42 W) compared with the healthy control group (167 ± 53 W, p <0.001) but better than the CHD control group (124 ± 39 W, p = 0.023). Patients with MINOCA had lower physical and mental component summary scores compared with the healthy controls (p <0.001) and lower mental component summary (p = 0.012), mental health (p = 0.016), and vitality (p = 0.008) scores compared with the CHD controls. In conclusion, the findings of this first study on exercise capacity and QoL in patients with MINOCA showed both physical and mental distress from 6 weeks to 3 months after the acute event similar to CHD controls and in some perspectives even lower scores especially in the mental component of QoL.
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| 2. |
- Ekenbäck, Christina, et al.
(författare)
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Coronary microvascular dysfunction in Takotsubo syndrome and associations with left ventricular function
- 2023
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Ingår i: ESC Heart Failure. - 2055-5822. ; 10:4, s. 2395-2405
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Coronary microvascular dysfunction (CMD) has been proposed as an important pathophysiological mechanism in Takotsubo syndrome (TTS). Our aims were (i) to evaluate and compare levels of CMD in patients with TTS and patients with ischaemia and no obstructive coronary arteries (INOCA) and (ii) to investigate associations between CMD and clinical parameters, left ventricular function, and coronary atherosclerosis in TTS. Methods and results: We conducted a prospective study of 27 female TTS patients and an equally sized, age- and gender-matched, cohort of INOCA patients. Coronary microvascular function was quantified invasively using the index of microcirculatory resistance (IMR), coronary flow reserve (CFR), and resistive reserve ratio (RRR). CMD was defined as IMR ≥ 25 and/or CFR ≤ 2. In the TTS patients, left ventricular function was assessed with echocardiography and cardiovascular magnetic resonance (CMR) imaging, and coronary atherosclerosis was visualized with intravascular ultrasound with near-infrared spectroscopy (IVUS-NIRS). The incidence of CMD was higher in the TTS patients than in the INOCA cohort (78% vs. 44%, P = 0.01), with higher IMR (30 vs. 14, P = 0.002), lower CFR (1.8 vs. 2.8, P = 0.009), and lower RRR (2.1 vs. 3.5, P = 0.003). In apical compared with midventricular TTS, IMR was numerically higher (50 vs. 28, P = 0.20), whereas CFR and RRR were lower (1.5 vs. 2.5, P = 0.003 and 1.6 vs. 2.7, P = 0.01, respectively). Global longitudinal strain and global circumferential strain, assessed with CMR imaging, were more impaired in apical than in midventricular TTS (−11 vs. −14, P < 0.001 and −12 vs. −15, P = 0.049, respectively). In the TTS patients, CFR and RRR correlated with echocardiography-derived (R2 = 0.15, P = 0.002 and R2 = 0.18, P = 0.007, respectively) and CMR-derived (R2 = 0.09, P = 0.025 and R2 = 0.10, P = 0.038, respectively) ejection fraction. CFR and RRR correlated inversely with CMR-derived end-diastolic volume index, end-systolic volume index, and left ventricular mass index. IMR, CFR, and RRR were not associated with measures of coronary atherosclerosis derived by IVUS-NIRS. Conclusions: Coronary microvascular dysfunction is common in patients with TTS and more frequent than in patients with INOCA. CMD in TTS is more severe in the apical compared with the midventricular phenotype of the syndrome, is associated with left ventricular function, but is unrelated to coronary atherosclerosis. Our results support the notion of CMD as a key mediator in TTS.
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| 3. |
- Ekenbäck, Christina
(författare)
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Pathophysiology of myocardial infarction with non-obstructive coronary arteries and Takotsubo syndrome
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The working diagnosis myocardial infarction with non-obstructive coronary arteries (MINOCA), with the subgroup myocardial infarction with normal coronary arteries (MINCA), encompasses conditions of diverse aetiological origin. One of them is Takotsubo syndrome (TTS), a reversible and often stress-induced condition of acute heart failure, predominantly affecting postmenopausal women. Both MINOCA and TTS are associated with substantial morbidity and mortality, yet evidence-based treatment is lacking. The overall aim of this thesis was to expand the knowledge on pathophysiological mechanisms of MINOCA and TTS, with a view to guide future clinical management. The study specific aims were I) to characterise MINCA patients regarding risk factors and markers for endothelial function and atherosclerosis, II) to improve the diagnostics of MINOCA, III) to study if coronary microvascular dysfunction (CMD) is a prominent feature of acute TTS, and whether CMD in TTS is associated with clinical parameters, and IV) to determine whether sympathetic activity and reactivity are enhanced in the early recovery phase of TTS. Methods and results: In study I, the first Stockholm Myocardial Infarction with Normal Coronaries (SMINC) study, we included 100 MINCA patients together with two age- and sexmatched control groups of MI patients with coronary heart disease, respectively healthy volunteers. Endothelial function was evaluated with peripheral arterial tonometry measuring reactive hyperaemia index. Atherosclerosis was evaluated with carotid ultrasound measuring intima-media thickness. MINCA was associated with many established cardiovascular risk factors and female sex. Measures of endothelial function and atherosclerosis did not differ between study groups. One out of four MINCA patients received a clinical diagnosis of TTS. In study II, the SMINC-2 study, 148 MINOCA patients were examined by comprehensive cardiovascular magnetic resonance (CMR) imaging at median 3 days after admission. 150 patients from the screening phase of the SMINC-1 study, examined by standard CMR imaging at median 12 days after admission, served as historical controls. The underlying diagnosis was identified in 77% of patients in the SMINC-2 study, compared to 47% of patients in SMINC-1. The improved diagnostic yield was mainly due to increased detection of myocarditis and TTS. In study III, the Sympathetic And vascular Function in Takotsubo syndrome (SAFT) study, we included 27 female TTS patients together with age- and sexmatched controls with ischemia and no obstructive coronary arteries (INOCA). CMD was assessed invasively with thermodilution technique during index coronary angiography. Cardiac function was determined by echocardiography and CMR imaging in TTS patients. CMD was more common in TTS patients than in INOCA controls (78% vs. 44%). CMD was related to left ventricular function in TTS and more pronounced in the apical than midventricular phenotype. In study IV, muscle sympathetic nerve activity (MSNA) was determined by microneurography of the peroneal nerve at rest and during stress in 18 TTS patients from the SAFT study together with 13 age- and sex-matched healthy controls. Cardiac specific sympathetic activity was depicted by 123Imetaiodobenzylguanidine scintigraphy in 10 TTS patients. Despite signs of increased cardiac sympathetic activity in TTS, MSNA at rest and in response to stress did not differ between TTS patients and controls. Conclusions: MINCA is associated with many cardiovascular risk factors, female sex, and TTS, but not with markers of endothelial function and atherosclerosis. Early and comprehensive CMR imaging significantly improves the diagnostic yield in MINOCA and is therefore strongly suggested as a standard diagnostic tool. CMD is highly prevalent in the acute phase of TTS, associated with left ventricular function, and thus proposed as a key mediator in TTS pathophysiology. An altered cardiac response to sympathetic activation, rather than an underlying sympathetic hyperactivity or hyperreactivity, is likely central for TTS development.
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| 4. |
- Hjort, Marcus, et al.
(författare)
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Increased Inflammatory Activity in Patients 3 Months after Myocardial Infarction with Nonobstructive Coronary Arteries
- 2019
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Ingår i: Clinical Chemistry. - : AMER ASSOC CLINICAL CHEMISTRY. - 0009-9147 .- 1530-8561. ; 65:8, s. 1023-1030
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Around 5%-10% of patients with myocardial infarction (MI) present with nonobstructive coronary arteries (MINOCA). We aimed to assess pathophysiological mechanisms in MINOCA by extensively evaluating cardiovascular biomarkers in the stable phase after an event, comparing MINOCA patients with cardiovascular healthy controls and MI patients with obstructive coronary artery disease (MI-CAD).METHODS: Ninety-one biomarkers were measured with a proximity extension assay 3 months after MI in 97 MINOCA patients, 97 age-and sex-matched MI-CAD patients, and 98 controls. Lasso analyses (penalized logistic regression models) and adjusted multiple linear regression models were used for statistical analyses.RESULTS: In the Lasso analysis (MINOCA vs MI-CAD), 8 biomarkers provided discriminatory value: P-selectin glycoprotein ligand 1, C-X-C motif chemokine 1, TNF-related activation-induced cytokine, and pappalysin-1 (PAPPA) with increasing probabilities of MINOCA, and tissue-type plasminogen activator, B-type natriuretic peptide, myeloperoxidase, and interleukin-1 receptor antagonist protein with increasing probabilities of MI-CAD. Comparing MINOCA vs controls, 7 biomarkers provided discriminatory value: N-terminal pro-B-type natriuretic peptide, renin, NF-kappa-B essential modulator, PAPPA, interleukin-6, and soluble urokinase plasminogen activator surface receptor with increasing probabilities of MINOCA, and agouti-related protein with increasing probabilities of controls. Adjusted multiple linear regression analyses showed that group affiliation was associated with the concentrations of 7 of the 8 biomarkers in the comparison MINOCA vs MI-CAD and 5 of the 7 biomarkers in MINOCA vs controls.CONCLUSIONS: Three months after the MI, the biomarker concentrations indicated greater inflammatory activity in MINOCA patients than in both MI-CAD patients and healthy controls, and a varying degree of myocardial dysfunction among the 3 cohorts.
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| 5. |
- Nero, Daniella, et al.
(författare)
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Personality Traits in Patients with Myocardial Infarction with Nonobstructive Coronary Arteries.
- 2019
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Ingår i: The American journal of medicine. - : Elsevier BV. - 1555-7162 .- 0002-9343. ; 132:3, s. 374-381
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to describe type A behavior pattern and trait anger in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) and compare them with patients with coronary heart disease and healthy controls. Type A behavior pattern and anger have been linked to coronary heart disease in previous studies. This is the first study to assess type A behavior pattern and trait anger in MINOCA patients.One hundred MINOCA patients, consecutively recruited during 2007-2011 at 5 coronary care units in Stockholm, were matched for sex and age to 100 coronary heart disease patients and 100 healthy controls. All participants completed the Bortner Rating Scale to quantify type A behavior pattern and the Spielberger Trait Anger Scale to quantify anger 3 months after the acute event.MINOCA patients' Bortner Rating Scale score was 70.9 ± 10.8 (mean ± SD) and Spielberger Trait Anger Scale score was 14 (12-17) (median; interquartile range). Coronary heart disease patients' Bortner Rating Scale score was 70.5 ± 10.2 and Spielberger Trait Anger Scale score was 14 (12-17). Healthy controls' Bortner Rating Scale score was 71.9 ± 9.1 and Spielberger Trait Anger Scale score was 13 (11-16).We found no significant differences in Bortner Rating Scale score and Spielberger Trait Anger Scale score among MINOCA, coronary heart disease patients, and healthy controls, regardless of whether total scores, subscales, or cutoffs were used to classify type A behavior pattern and trait anger. However, we cannot exclude the existence of an occasional episode of anger or mental stress in relation to the coronary event. This is the first study to assess type A behavior pattern and trait anger in patients with MINOCA, and future studies need to confirm the current findings before any firm conclusions can be made.
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| 6. |
- Omerovic, Elmir, et al.
(författare)
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Rationale and design of BROKEN-SWEDEHEART : a registry-based, randomized, parallel, open-label multicenter trial to test pharmacological treatments for broken heart (takotsubo) syndrome
- 2023
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 257, s. 33-40
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Tidskriftsartikel (refereegranskat)abstract
- Background: Takotsubo syndrome (TS) is a life-threatening acute heart failure syndrome without any evidence-based treatment options. No treatment for TS has been examined in a randomized trial.Study design and objectives: BROKEN-SWEDEHEART is a multicenter, randomized, open-label, registry-based 2 × 2 factorial clinical trial in patients with TS designed to test whether treatment with adenosine and dipyridamole accelerates cardiac recovery and improves clinical outcomes compared to standard care (study 1); and apixaban reduces the risk of thromboembolic events compared to no treatment with antithrombotic drugs (study 2). The trial will enroll 1,000 patients. Study 1 (adenosine hypothesis) will evaluate 2 coprimary end points: (1) wall motion score index at 48 to 96 hours (evaluated in the first 200 patients); and (2) the composite of death, cardiac arrest, need for mechanical assist device or heart failure hospitalization within 30 days or left ventricular ejection fraction <50% at 48 to 96 hours (evaluated in 1,000 patients). The primary end point in study 2 (apixaban hypothesis) is the composite of death or thromboembolic events within 30 days or the presence of intraventricular thrombus on echocardiography at 48 to 96 hours.Conclusions: BROKEN-SWEDEHEART will be the first prospective randomized multicenter trial in patients with TS. It is designed as 2 parallel studies to evaluate whether adenosine accelerates cardiac recovery and improves cardiac function in the acute phase and the efficacy of anticoagulation therapy for preventing thromboembolic complications in TS. If either of its component studies is successful, the trial will provide the first evidence-based treatment recommendation in TS.Clinical trials identifier: The trial has been approved by the Swedish Medicinal Product Agency and the Swedish Ethical Board and is registered at ClinicalTrials.gov (NCT04666454).
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| 7. |
- Omerovic, Elmir, 1968, et al.
(författare)
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Rationale and design of BROKEN-SWEDEHEART: a registry-based, randomized, parallel, open-label multicenter trial to test pharmacological treatments for broken heart (takotsubo) syndrome.
- 2022
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Ingår i: American heart journal. - : Elsevier BV. - 1097-6744 .- 0002-8703.
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Tidskriftsartikel (refereegranskat)abstract
- Takotsubo syndrome (TS) is a life-threatening acute heart failure syndrome without any evidence-based treatment options. No treatment for TS has been examined in a randomized trial.design and objectives BROKEN-SWEDEHEART is a multicenter, randomized, open-label, registry-based 2 × 2 factorial clinical trial in patients with TS designed to test whether treatment with adenosine and dipyridamole accelerates cardiac recovery and improves clinical outcomes compared to standard care (study 1); and apixaban reduces the risk of thromboembolic events compared to no treatment with antithrombotic drugs (study 2). The trial will enroll 1000 patients. Study 1 (adenosine hypothesis) will evaluate two co-primary endpoints: (1) wall motion score index at 48-96 hours (evaluated in the first 200 patients); and (2) the composite of death, cardiac arrest, need for mechanical assist device or heart failure hospitalization within 30 days or left ventricular ejection fraction <50% at 48-96 hours (evaluated in 1000 patients). The primary endpoint in study 2 (apixaban hypothesis) is the composite of death or thromboembolic events within 30 days or the presence of intraventricular thrombus on echocardiography at 48-96 hours.BROKEN-SWEDEHEART will be the first prospective randomized multicenter trial in patients with TS. It is designed as two parallel studies to evaluate whether adenosine accelerates cardiac recovery and improves cardiac function in the acute phase and the efficacy of anticoagulation therapy for preventing thromboembolic complications in TS. If either of its component studies is successful, the trial will provide the first evidence-based treatment recommendation in TS.
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| 8. |
- Redfors, Björn, et al.
(författare)
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Short- and Long-Term Clinical Outcomes for Patients With Takotsubo Syndrome and Patients With Myocardial Infarction : A Report From the Swedish Coronary Angiography and Angioplasty Registry
- 2021
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980 .- 2047-9980. ; 10:17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Takotsubo syndrome (TS) is a potentially life-threatening acute cardiac syndrome with a clinical presentation similar to myocardial infarction and for which the natural history, management, and outcome remain incompletely understood. Our aim was to assess the relative short-term mortality risk of TS, ST-segment-elevation myocardial infarction (STEMI), and non-STEMI (NSTEMI) and to identify predictors of in-hospital complications and poor prognosis in patients with TS.Methods and Results: This is an observational cohort study based on the data from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry). We included all patients (n=117 720) who underwent coronary angiography in Sweden attributed to TS (N=2898 [2.5%]), STEMI (N=48 493 [41.2%]), or NSTEMI (N=66 329 [56.3%]) between January 2009 and February 2018. We compared patients with TS to those with NSTEMI or STEMI. The primary end point was all-cause mortality at 30 days. Secondary outcomes were acute heart failure (Killip Class ≥2) and cardiogenic shock (Killip Class 4) at the time of angiography. Patients with TS were more often women compared with patients with STEMI or NSTEMI. TS was associated with unadjusted and adjusted 30-day mortality risks lower than STEMI (adjusted hazard ratio [adjHR], 0.60; 95% CI, 0.48-0.76; P<0.001), but higher than NSTEMI (adjHR, 2.70; 95% CI, 2.14-3.41; P<0.001). Compared with STEMI, TS was associated with a similar risk of acute heart failure (adjHR, 1.26; 95% CI, 0.91-1.76; P=0.16) but a lower risk of cardiogenic shock (adjHR, 0.55; 95% CI, 0.34-0.89; P=0.02). The relative 30-day mortality risk for TS versus STEMI and NSTEMI was higher for smokers than nonsmokers (adjusted P interaction STEMI=0.01 and P interaction NSTEMI=0.01). Conclusions: The 30-day mortality rate in TS was higher than in NSTEMI but lower than STEMI despite a similar risk of acute heart failure in TS and STEMI. Among patients with TS, smoking was an independent predictor of mortality.
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| 9. |
- Svenungsson, Elisabet, et al.
(författare)
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Antiphospholipid antibodies in patients with myocardial infarction with and without obstructive coronary arteries
- 2022
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 291:3, s. 327-337
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent studies demonstrate that prothrombotic antiphospholipid antibodies (aPL) are overrepresented in patients with myocardial infarction (MI) due to coronary artery disease (MICAD). However, it is not known whether aPL differ between the two subsets of MI: MICAD and MI with nonobstructive coronary arteries (MINOCA). Objectives: To determine whether aPL are associated with MINOCA or MICAD, or with hypercoagulability as assessed by activated protein C–protein C inhibitor (APC–PCI) complex. Methods: Well-characterized patients with MINOCA (n = 98), age- and gender-matched patients with MICAD (n = 99), and healthy controls (n = 100) were included in a cross-sectional case–control study. Autoantibodies (IgA/G/M) targeting cardiolipin and β2glycoprotein-I and specific nuclear antigens were analyzed by multiplexed bead technology. The concentration of APC–PCI was determined as a measure of hypercoagulability by an immunofluorometric sandwich assay. Results: Both prevalence and titers of aPL of the IgG isotype (anti-cardiolipin and/or anti-β2glycoprotein-I) were higher in patients with MINOCA and MICAD than in controls. aPL IgG positivity was twice as frequent among patients with MICAD than MINOCA (11% vs. 6%, nonsignificant). We observed no group differences regarding aPL IgA/M or antibodies targeting specific nuclear antigens. Levels of APC–PCI were elevated in aPL IgG-positive compared to aPL IgG-negative MICAD patients. Conclusions: aPL IgG, but not IgA/M, are enriched particularly in patients with MICAD but also in patients with MINOCA, as compared to controls. Interestingly, signs of hypercoagulability—measured by increased levels of the APC–PCI complex—were present in aPL IgG-positive MICAD patients, indicating an association with functional disturbances of the coagulation system.
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